Small RNAs are raising big expectations.

F ive years ago there were little more than 200 known microRNAs (miRNAs) — small regulatory nucleic acids that bind to complementary sites on mRNAs and prevent their translation into protein. Today, that number has swelled to more than 700 and counting. The explosion in knowledge about these small, noncoding RNAs, which appear to be evolutionarily ancient but were discovered less than two decades ago, has already led to the marketing of new cancer diagnostic tools and, researchers say, may eventually lead to treatments. Take the case of “cancers of unknown primary” (CUPs) — cancers that clearly originated in another, unknown site. CUPs account for about 3% of diagnoses according to Robert Hromas, M.D., chief of oncology services at the University of New Mexico Cancer Research and Treatment Center in Albuquerque. Using a new miRNA-based test, physicians can now identify the site that the CUP tumor came from, Hromas said, allowing them to choose an appropriate chemotherapy regimen. That test is one of three new miRNA-based cancer diagnostic tests now marketed by Rosetta Genomics in Rehovet, Israel, a diagnostics company with a U.S.-based testing facility in Philadelphia. The tests are designed to differentiate cancers on the basis of the levels of a subset of miRNA associated with a particular form of cancer. Clinical testing, which was just completed for at least one of the tests, showed that miRNA profi ling distinguished squamous cell lung carcinomas from other non – small-cell lung cancers with 96% sensitivity and 90% specifi city in 122 adenocarcinoma and squamous cell carcinoma samples. The Rosetta tests may be the fi rst in a wave of miRNA-based assays. At the American Association for Cancer Research (AACR) meeting in April, more than 200 posters and presentations contained data linking miRNA to just about every known form of cancer. Researchers say they hold promise now, not only as diagnostics but also as prognostic biomarkers.